Indeed, therapies targeting TNF have shown promising results in improving nonalcoholic steatohepatitis in humans.4, 5 However, by contrast, anti‐TNF therapy has not been successful in ameliorating alcoholic hepatitis6 and, unexpectedly, can even trigger reactivation of hepatitis B virus infection by preventing viral clearance.7 Thus, dissection of the TNF/TNF receptor 1 (TNFR1) system in distinct etiologies and cell types is crucial to improve the strategy for intervention of liver diseases. This evidence concerns the gene TNF and metabolic dysfunction-associated steatohepatitis.